Trifluoroacetic acid → HCID 178424542, compound

Participants

Reaction Steps

A flask was charged with 4-[(4-cyano-1H-imidazole-2-carbonyl)-amino]-3-(4,4-dimethyl-cyclohex-1-enyl)-benzoic acid (36 mg, 99 μmol)(prepared in Example 65), L-glutamic acid diethyl ester hydrochloride (26 mg, 120 μmol), N-(3-dimethylamino-propyl)-N′-ethylcarbodiimide (23 mg, 120 μmol), 1-hydroxybenzotriazole (13 mg, 99 μmol), DIEA (38 mg, 300 μmol) and 0.3 mL of DCM and stirred for 8 h at RT. The mixture was diluted with 20 mL EtOAc, washed with NaHCO3 (2×20 mL) and brine (20 mL), and the organic layer was dried (Na2SO4) and concentrated. The residue was dissolved in 2 mL of EtOH and a 7 N aqueous KOH solution (43 μL, 300 μmol) was added and the reaction stirred for 8 h at RT. The pH was adjusted to 2 with a 2 N TFA solution and the title compound was purified by RP-HPLC eluting with a linear gradient of 30% to 50% acetonitrile in 0.1% TFA/H2O over 10 min on a C18 column giving 25 mg (52%) of a white solid. 1H-NMR (CD3OD, 400 MHz): δ 8.35 (d, J=8.6 Hz, 1H), 7.92 (s, 1H), 7.72 (dd, J=8.6, 2.1 Hz, 1H), 7.66 (d, J=2.1 Hz, 1H), 5.74 (m, 1H), 4.54 (m, 1H), 2.39 (t, J=7.4 Hz, 2H), 2.30-2.16 (m, 3H), 2.07-1.95 (m, 3H), 1.54 (t, J=6.3 Hz, 2H), 1.03 (s, 6H). Mass spectrum (ESI, m/z): Calcd. for C25H27N5O6, 494.2 (M+H), found 494.1.

Provenance & Evidence